title: A mathematical model of pulse-coded hormone signal responses in pituitary gonadotroph cells.
abstract: Cells in the pituitary that synthesize luteinizing and follicle-stimulating hormones regulate the relative production of these two key reproductive hormones in response to signals from the hypothalamus. These signals are encoded in the frequency of gonadotrophin-releasing-hormone pulses. In vitro experiments with a murine-derived cell line have identified key elements of the processes that decode the signal to regulate transcription of the subunits encoding these hormones. The mathematical model described in this paper is based on the results of those experiments and advances quantitative understanding of the biochemical decoder. The model consists of non-linear differential equations for each of six processes that lead to the synthesis of follicle-stimulating hormone. Simulations of the model exhibit key characteristics found in the experiments, including a preference for follicle-stimulating hormone synthesis at low pulse frequencies and a loss of this characteristic when a mutation is introduced.
authors.affiliation: Physical Sciences Inc., 20 New England Business Center, Andover, MA 01810-1077, USA. Electronic address: magill@psicorp.com.
authors.forename: John C
authors.initials: JC
authors.lastname: Magill
authors.forename: Nick A
authors.initials: NA
authors.lastname: Ciccone
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
mesh_terms: D000818:Animals; D003198:Computer Simulation; D052681:Gonadotrophs / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006801:Humans; D008962:Models, Theoretical; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007987:Gonadotropin-Releasing Hormone
keywords: CRE; CRE binding protein, a transcription factor that binds to a CRE site, modulating transcription of the associated gene; CREB; CREM; Cell signaling; Control theory; Endocrinology; FSH; GnRH; ICER; LH; Mathematical modeling; cAMP response element, a site in a gene promoter associated with the response to cyclic adenosine monophosphate (cAMP); follicle-stimulating hormone, a hormone produced by the pituitary that promotes the growth and development of follicles. The hormone is composed of two subunits, α and β; gene that codes for the ICER family of proteins; gonadotrophin-releasing-hormone; inducible cAMP early repressor, a protein involved in the regulation of FSHβ transcription; luteinizing hormone, a hormone produced by the pituitary that triggers ovulation